Trial Outcomes & Findings for Intensive Glycemic Control for Congestive Heart Failure Exacerbation (NCT NCT00812253)

NCT ID: NCT00812253

Last Updated: 2018-01-02

Results Overview

Duration of hospitalization in days

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 74 participants
• Primary outcome timeframe: Days
• Results posted on: 2018-01-02

Participant Flow

Participant milestones

Measure	Intravenous Insulin (IV) Intravenous insulin: In patients assigned to intravenous (IV) insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous Insulin Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Overall Study STARTED	32	42
Overall Study COMPLETED	26	39
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Measure	Intravenous Insulin (IV) Intravenous insulin: In patients assigned to intravenous (IV) insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous Insulin Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Overall Study Withdrawal by Subject	3	2
Overall Study Protocol Violation	1	1
Overall Study Lost to Follow-up	2	0

Baseline Characteristics

Intensive Glycemic Control for Congestive Heart Failure Exacerbation

Baseline characteristics by cohort

Measure	Intravenous (IV) Insulin n=26 Participants Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous (SQ) Insulin n=39 Participants Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.	Total n=65 Participants Total of all reporting groups
Age, Continuous	61 years STANDARD_DEVIATION 10 • n=5 Participants	63 years STANDARD_DEVIATION 12 • n=7 Participants	62 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	26 Participants n=7 Participants	44 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	39 participants n=7 Participants	65 participants n=5 Participants
Preserved ejection fraction Preserved Ejection Fraction	6 participants n=5 Participants	11 participants n=7 Participants	17 participants n=5 Participants
Preserved ejection fraction Reduced Ejection Fraction	20 participants n=5 Participants	28 participants n=7 Participants	48 participants n=5 Participants
HbA1c	8.4 Percentage of hemoglobin STANDARD_DEVIATION 2.0 • n=5 Participants	7.7 Percentage of hemoglobin STANDARD_DEVIATION 1.4 • n=7 Participants	8.0 Percentage of hemoglobin STANDARD_DEVIATION 1.7 • n=5 Participants

PRIMARY outcome

Timeframe: Days

Duration of hospitalization in days

Outcome measures

Measure	Intravenous (IV) Insulin n=26 Participants Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous (SQ) Insulin n=39 Participants Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Hospital Length of Stay	7 days Interval 5.0 to 11.0	8 days Interval 5.0 to 12.0

SECONDARY outcome

Timeframe: 30 days

All-cause hospital readmission at 30 days after discharge

Outcome measures

Measure	Intravenous (IV) Insulin n=26 Participants Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous (SQ) Insulin n=39 Participants Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Hospital Readmission Readmitted	7 participants	15 participants
Hospital Readmission Not readmitted	19 participants	24 participants

SECONDARY outcome

Timeframe: 72 hours

Population: Subjects with medical devices, conditions that preclude measurement of HRV such as arrhythmias, or technical problems could not be analyzed.

High frequency (HF) Heart rate variability (HRV). HRV was assessed with a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration and impedance cardiography was performed using a standard tetrapolar arrangement. Measures were performed at baseline and each morning (0800-1000 hour) during and following the intervention for 7 minutes each. Software (Mindware, Gahanna, OH) was used to derive HF HRV. The middle five minutes of the recordings were scored minute by minute and the first suitable1 minute period was used for calculation. Five minute epochs were not feasible due to an unexpectedly high frequency of ectopy. One minute intervals allow calculation of HF (parasympathetic tone) but not low frequency (combination of sympathetic and parasympathetic tone).

Outcome measures

Measure	Intravenous (IV) Insulin n=12 Participants Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous (SQ) Insulin n=10 Participants Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Heart Rate Variability	5.1 ms^2 Interval 2.26 to 14.8	20.7 ms^2 Interval 4.92 to 312.9

SECONDARY outcome

Timeframe: 30 day

Change in Quality of Life questionnaire measured from baseline (enrollment) to 30 days following discharge. The questionnaire is a self-administered disease-specific questionnaire for patients with HF, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on health related quality of life, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst HRQoL),

Outcome measures

Measure	Intravenous (IV) Insulin n=19 Participants Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous (SQ) Insulin n=35 Participants Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Change in Quality of Life	-22.4 units on a scale Standard Deviation 22.0	-22.6 units on a scale Standard Deviation 26.3

SECONDARY outcome

Timeframe: 72 hours

Brain natriuretic peptide (BNP) was measured at day 3

Outcome measures

Measure	Intravenous (IV) Insulin n=26 Participants Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous (SQ) Insulin n=39 Participants Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Brain Natriuretic Peptide (BNP)	794 pg/ml Interval 168.0 to 1090.0	356 pg/ml Interval 192.0 to 910.0

SECONDARY outcome

Timeframe: 72 hours

Population: Patients without data due to medical devices, conditions that preclude measurement of PEP such as arrhythmias, or technical problems.

Cardiac output measured using impedance cardiography at 72 hours.

Outcome measures

Measure	Intravenous (IV) Insulin n=13 Participants Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous (SQ) Insulin n=11 Participants Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Cardiac Output	10.3 liter/min Standard Deviation 9.3	8.6 liter/min Standard Deviation 3.5

Adverse Events

Intravenous (IV) Insulin

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Subcutaneous (SQ) Insulin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Intravenous (IV) Insulin n=26 participants at risk Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Subcutaneous (SQ) Insulin n=39 participants at risk Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Endocrine disorders Hypoglycemia	34.6% 9/26 • 72 hours after enrollment	7.7% 3/39 • 72 hours after enrollment

Additional Information

Kathleen Dungan

The Ohio State University

Phone: 6146853333

Email: kathleen.dungan@osumc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place